Anticancer effects of 7,8-dihydromethysticin in human leukemia cells are mediated via cell-cycle dysregulation, inhibition of cell migration and invasion and targeting JAK/STAT pathway

The main focus of this research work was to study the anticancer properties of 7,8-dihydromethysticin against HL-60 leukemia cells. Investigations were also performed to check its impact on the phases of the cell cycle, cell migration and invasion, JAK/STAT signalling pathway and intracellular mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Cell proliferation was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and effects on colony formation were examined via clonogenic assay. Flow cytometry and western blott analysis were performed to investigate the distribution of cell cycle phases. Flow cytometric analysis was performed for the examination of MMP and ROS production. The effect on JAK/STAT signalling pathway was examined through western blot analysis. Results depicted that 7,8-dihydromethysticin induced concentration- as well as time-dependent inhibition of cell proliferation in leukemia HL-60 cells. Clonogenic assay indicated potential suppression in leukemia HL-60 cell colonies. The 7,8-dihydromethysticin molecule also caused cell cycle arrest at G2/M-phase along with concentration-dependent inhibition of cyclin B1, D1 and E. ROS and MMP measurements indicated significant ROS enhancement and MMP suppression with increasing 7,8-dihydromethysticin concentrations. Additionally, 7,8-dihydromethysticin led to remarkable dose-reliant inhibition of cell invasion as well as cell migration. Therefore, 7,8-dihydromethysticin should be considered a valuable candidate for leukemia research and chemoprevention

1286391_Table 1_Associations between urinary phthalate concentrations and antral follicle count among women undergoing in vitro fertilization.docx

BackgroundPhthalates are ubiquitously used in a variety of products and have an adverse effect on folliculogenesis. However, previous epidemiological studies on the associations between phthalate exposure and antral follicle count (AFC) produced conflicting results. The present study aimed to evaluate the associations between urinary phthalate metabolite concentrations and AFC among women undergoing in vitro fertilization (IVF).MethodsWe collected 525 urine samples and measured 8 phthalate metabolites from IVF patients. Poisson regression models were conducted to evaluate the associations between phthalate metabolite concentrations and AFC. In addition, participants were stratified into a younger group (ResultsSignificant positive associations were observed among urinary MBP, MEOHP and ∑PAEs concentrations and AFC after adjusting for age, BMI, year of study and infertility diagnosis. Compared with women in the first tertile, women in the third tertile of MBP and MEOHP had 7.02% (95% CI: 1.18%, 12.9%) and 8.84% (95% CI: 2.83%, 14.9%) higher AFC, respectively, and women in the second and third tertiles of ∑PAEs had 6.19% (95% CI: 0.37%, 12.0%) and 9.09% (95% CI: 3.22%, 15.0%) higher AFC, respectively. In addition, MBP, MEOHP and ∑PAEs also had significant positive associations with AFC in trend tests for dose-response. In the age-stratified analysis, we found a stronger relationship between phthalate metabolite concentrations and AFC among older women and an inverse association among younger women. We observed similar results in the sensitivity analyses.ConclusionWe found positive associations between phthalate exposure and AFC, which support the idea that phthalate exposure may accelerate primordial follicle recruitment and lead to higher AFC in women undergoing IVF. More studies are needed to better understand their relationships.</p

Biological soil crust succession in deserts through a 59-year-long case study in China: How induced biological soil crust strategy accelerates desertification reversal from decades to years

The regeneration of induced biological soil crusts (IBSCs) is regarded as an effective strategy for combating desertification. Three types of BSCs, namely, cyanobacterial, lichen and moss, are well-accepted as the main succession phases and are hypothesized to represent a continuous process. Herein, natural BSCs (NBSCs) and IBSCs with accurate ages from a 59-year-long field study were investigated to understand the entire BSC succession process. Shifts in nutrient levels, microbial composition and ecological functions suggested that cyanobacterial inoculation successfully accelerated BSC succession from decades to years by promoting the microbial multifunctions related to carbon and nitrogen fixation. The four state transitions of the BSC community accompanied by the turn-over of carbon and nitrogen fixators provide clues to the factors restricting the recovery process and climax of arid ecosystems. This study provides the first description of the continuous BSC succession, comprehensively discusses the mechanisms of BSC formation and succession and provides important guides for selection of strategies for the engineering reversals of desertification

Phthalate metabolites in urine and follicular fluid in relation to menstrual cycle characteristics in women seeking fertility assistance

Background: Phthalates have been shown to disrupt the estrous cycle in animal studies. However, epidemiological research investigating their associations with menstrual cycle characteristics is limited. Objective: To explore the relationships between phthalate exposure and menstrual cycle characteristics among women seeking fertility assistance. Methods: We determined the levels of eight phthalate metabolites in both follicular fluid (FF) and urine specimens collected from 441 women in the Tongji Reproductive and Environmental (TREE) cohort, using high-performance liquid chromatography and tandem mass spectrometry. Information about menstrual cycle parameters was obtained through a questionnaire. The impacts of individual and joint exposure to phthalates on menstrual cycle characteristics were assessed using multivariable linear regression, Poisson regression, and quantile g-computation approaches. Results: After adjusting for relevant covariates, we found that per log10-unit increase in mono(2-ethylhexyl) phthalate (MEHP) level in urine specimens was associated with a decrease of 0.20 days (95 % CI: −0.37, −0.03) in bleeding duration. We also observed that mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and the sum of di(2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHP) concentrations in FF samples were inversely related to cycle length [β = −1.92 (95 % CI: −3.10, −0.75) and −1.87 (95 % CI: −3.56, −0.19), respectively]. However, we generally observed null associations between phthalate metabolites and irregular cycle, dysmenorrhea, hypomenorrhea, or cycle length variation. Furthermore, we also found that phthalate metabolite mixtures in FF and urine were generally unrelated to menstrual cycle characteristics. Conclusion: Our findings suggest that some DEHP metabolites in FF and urine are inversely associated with menstrual cycle length and menstrual bleeding duration in women attending a fertility center

Improved detection of homologous recombination deficiency in Chinese patients with ovarian cancer: a novel non‐exonic single‐nucleotide polymorphism‐based next‐generation sequencing panel

As homologous recombination deficiency (HRD) is a biomarker to predict the efficiency of PARP inhibitor treatment, this study developed a non‐exonic single‐nucleotide polymorphism (SNP)‐based targeted next‐generation sequencing panel and comprehensively examined it both on standard and clinical ovarian cancer tissues. The HRD scores calculated by the panel and whole‐genome sequencing were consistent, with the analysis by sequenza being the most reliable. The results on clinical samples revealed that the panel performed better in HRD analysis compared with the SNP microarray. There are several distinctions between this newly developed kit and reported HRD detection panels. First, the panel covers only 52 592 SNPs, which makes it capable of detecting genomic instability. Secondly, all the SNPs are non‐exonic; as a result, the panel can be used cooperatively with any exon panel. Thirdly, all the SNPs selected have a high minor allele frequency in Chinese people, making it a better choice for HRD detection in Chinese patients. In summary, this panel shows promise as a clinical application to guide PARP inhibitors or platinum drugs used in the treatment of ovarian and other cancers